TY - JOUR T1 - How does ALS spread between neurones in the CNS? JF - Journal of Neurology, Neurosurgery & Psychiatry JO - J Neurol Neurosurg Psychiatry SP - 116 LP - 117 DO - 10.1136/jnnp-2012-303992 VL - 84 IS - 1 AU - Michael Swash Y1 - 2013/01/01 UR - http://jnnp.bmj.com/content/84/1/116.abstract N2 - In recent years, the concept of contiguous spread of the disease process in amyotrophic lateral sclerosis (ALS) has become more accepted,1 although how this might occur is still uncertain. Kanouchi et al 2 reviewed the extensive clinical, physiological and molecular evidence for this process in this journal, noting that ALS can be recognised to spread both contiguously and non-contiguously, the latter implying more than one focus of disease onset—a ‘skipping’ pattern of spread. They concluded that contiguous spread explains regional progression, but offered no explanation for the process of propagation itself. It has been suggested that cell-to-cell spread requires that abnormal cytosolic proteins in ALS, for example, TDP-43, which seems to underlie the ubiquitinated inclusions so characteristic of sporadic ALS, are misfolded, self-aggregate and form toxic proteinaceous inclusions with a β cross-conformation, resembling prions.3 A prion-like propagation process implies that the abnormal protein spreads to involve other nearby cells, whether neuronal or glial. Prusiner,4 from whose insight the prion … ER -